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Safety, Tolerability, Pharmacokinetics, and Immunoregulatory Study of Urelumab (BMS-663513) in Subjects With Advanced and/or Metastatic Solid Tumors and Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Bristol-Myers Squibb
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01471210
First received: November 10, 2011
Last updated: November 20, 2014
Last verified: July 2014
  Purpose

The purpose of the study is to assess the safety, tolerability, pharmacokinetics and immunoregulatory activity of urelumab (BMS-663513) in cancer subjects with advanced and/or metastatic tumors and relapsed/refractory B-Cell Non-Hodgkin's Lymphoma


Condition Intervention Phase
Cancer - Solid Tumors and B-Cell Non-Hodgkin's Lymphoma
Drug: Urelumab (BMS-663513)
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1 Study of the Safety, Tolerability, Pharmacokinetics and Immunoregulatory Activity of Urelumab (BMS-663513) in Subjects With Advanced and/or Metastatic Solid Tumors and Relapsed/Refractory B-cell Non-Hodgkin's Lymphoma (B-NHL)

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Safety assessments will be based on medical review of adverse event reports and the results of vital sign measurements, physical examinations, and clinical laboratory tests [ Time Frame: Every 3 weeks from Baseline (Day 1) for up to 2 years ] [ Designated as safety issue: Yes ]
    The incidence of adverse events will be tabulated and reviewed for potential significance and clinical Importance.

  • Dose-limiting toxicity and maximum tolerated dose of Urelumab (BMS-663513) as determined by the incidence of dose-limiting toxicities [ Time Frame: Every 3 weeks from Baseline (Day 1) for up to 9 weeks of therapy ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Maximum observed serum concentrations (Cmax) of Urelumab (BMS-663513) [ Time Frame: Cycle 1 Day 1 ] [ Designated as safety issue: No ]
  • Minimum observed serum concentrations (Cmin) of Urelumab (BMS-663513) [ Time Frame: Cycle 2 Day 1, Cycle 3 Day 1, every 12 weeks thereafter up to 2 years ] [ Designated as safety issue: No ]
  • Time of maximum observed serum concentration (Tmax) of Urelumab (BMS-663513) [ Time Frame: Cycle 1 Day 1 ] [ Designated as safety issue: No ]
  • Area under the concentration-time curve in 1 dosing interval [AUC(TAU)] of Urelumab (BMS-663513) [ Time Frame: Cycle 1 Day 1 - Day 4, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 3 Day 1 and every 12 weeks thereafter up to 2 years ] [ Designated as safety issue: No ]
  • Plasma half-life (T-HALF) of Urelumab (BMS-663513) [ Time Frame: Cycle 1 Day 1 - Day 4, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 3 Day 1 and every 12 weeks thereafter up to 2 years ] [ Designated as safety issue: No ]
  • Total body clearance (CLT) of Urelumab (BMS-663513) [ Time Frame: Cycle 1 Day 1 - Day 4, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 3 Day 1 and every 12 weeks thereafter up to 2 years ] [ Designated as safety issue: No ]
  • Volume of distribution at steady-state (Vss) of Urelumab (BMS-663513) [ Time Frame: Cycle 1 Day 1 - Day 4, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 3 Day 1 and every 12 weeks thereafter up to 2 years ] [ Designated as safety issue: No ]
  • Human Anti-human Antibodies [ Time Frame: Cycle 1 Day 1 - Day 4, Cycle 1 Day 8, Cycle 1 Day 15, Cycle 2 Day 1, Cycle 2 Day 8, Cycle 3 Day 1 and every 12 weeks thereafter up to 2 years ] [ Designated as safety issue: No ]
    Immunogenicity of Urelumab (BMS-663513), as determined by blood sample measurements of human antihuman antibodies (HAHA)

  • Tumor response and progression as determined by proportion of patients with best overall response (BOR), progression-free survival (PFS), objective response rate (ORR), time to response, and duration of response [ Time Frame: 9 weeks from Baseline (Day 1) and every 9 weeks until disease progression, death or last tumor assessment (Approximately up to 2 years) ] [ Designated as safety issue: No ]

Estimated Enrollment: 122
Study Start Date: February 2012
Estimated Study Completion Date: March 2019
Estimated Primary Completion Date: February 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Part 1 : Urelumab (BMS-663513) Dose escalation
Urelumab (BMS-663513) solution administered intravenously on specified days
Drug: Urelumab (BMS-663513)
Experimental: Part 2 : Urelumab (BMS-663513) Cohort Expansion
Urelumab (BMS-663513) solution administered intravenously on specified days
Drug: Urelumab (BMS-663513)
Experimental: Part 3:Urelumab (BMS-663513) Tumor-specific Cohort Expansions
Enrollment of subjects of three specific tumor types [(colorectal cancer (CRC), head and neck squamous cell carcinoma (SCCHN), and B-Cell non-Hodgkin's lymphoma (B-NHL)] who will be treated at the Maximum Tolerated Dose (MTD) (or highest dose tested)
Drug: Urelumab (BMS-663513)
Experimental: Part 4:Urelumab (BMS-663513) Cohort Expansion in B-NHL
Arm A and Arm B: Urelumab (BMS-663513) liquid administered intravenously on specified days exploring q3w and q6w dosing regimen
Drug: Urelumab (BMS-663513)

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com.

Inclusion Criteria:

  1. Signed Written Informed Consent

    • The signed informed consent form
  2. Target Population

    • Subjects with advanced and/or metastatic solid tumors or B-NHL who are either refractory to or have relapsed from standard therapies, or for whom a standard therapy does not exist with measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria
    • Life expectancy of 12 weeks or greater
    • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
    • Adequate organ and marrow function
    • For certain subjects, willing and able to provide pre- and post-treatment fresh tumor biopsies
  3. Age and Reproductive Status

    • Women of childbearing potential (WOCBP) and men must be using an acceptable method of contraception to avoid pregnancy throughout the study and for at least 4 weeks prior to initiation of dosing, and for at least 60 days after the last dose of investigational product in such a manner that the risk of pregnancy is minimized
    • WOCBP must have a negative serum or urine pregnancy test [minimum sensitivity 25 UI/L or equivalent units of human chorionic gonadotrophin (HCG)] within 24 hours prior to the start of investigational product
    • Women must not be breastfeeding

Exclusion Criteria:

  1. Target Disease Exceptions

    • Subjects with known or suspected brain metastasis unless previously treated and without evidence of progression
    • Subjects with a history of prior malignancy active within the previous 2 years except for locally curable cancers that have been apparently cured
    • Subjects with hepatocellular carcinoma
  2. Medical History and Concurrent Diseases

    • Any active autoimmune disease or documented history of autoimmune disease, or history of syndrome that required systemic steroids or immunosuppressive medications, except for subjects with vitiligo, psoriasis inactive within past 2 years, resolved childhood asthma/atopy, or thyroid disease controlled by replacement therapy without the need for immunosuppression
    • Known or suspected human immunodeficiency virus (HIV) or hepatitis A(acute), B or C infection
    • History of any hepatitis (e.g., alcohol or non-alcohol steatohepatitis (NASH), drug-related, auto-immune)
    • Evidence of active infection, requiring parenteral anti-bacterial, anti-viral or anti-fungal therapy < 7 days prior to administration of study medication
    • History of clinically significant cardiac disease, including but not limited to a history (personal or family) of congenital long QT syndrome
    • Grade > 1 QTc prolongation at baseline (> 450 msec by Bazett formula) confirmed by a repeat electrocardiogram (ECG)
    • History of myocardial infarction or uncontrolled angina within 12 months prior to administration of study drug
  3. Physical and Laboratory Test Findings

    • WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 12 weeks after the last dose of investigational product
    • Women who are pregnant or breastfeeding
    • Women with a positive pregnancy test on enrollment or prior to investigational product administration
    • Sexually active fertile men not using effective birth control if their partners are WOCBP
    • Positive blood screen for hepatitis A IgM, hepatitis C antibody, hepatitis B surface antigen, or HIV-1, -2 antibody
  4. Allergies and Adverse Drug Reaction

    • History of allergy to Urelumab (BMS-663513) or related compounds
    • History of significant drug allergy (such as anaphylaxis or hepatotoxicity) to a prior biologic therapy
  5. Prohibited Treatments and/or Therapies

    • The systemic use of the following therapies are prohibited within 28 days of first dose of study medication, or longer where indicated:

      1. Use of anti-cancer treatment (including investigational drugs) within 28 days
      2. Immunosuppressive medications or immunosuppressive doses of systemic corticosteroids
      3. Surgery (except minor surgeries,e.g., biopsies) or radiotherapy
      4. Any non-oncology live viral vaccine therapies used for the prevention of infectious diseases.
    • Prior treatment with anti-programmed death 1 (anti-PD-1)/Programmed cell death 1 ligand 1 (PD-L1) or anti-CD137
    • Any subject with the following reported drug-related adverse events on anti- Cytotoxic T-Lymphocyte Antigen 4 (anti-CTLA4) will not be permitted on study: hepatic, diarrhea/colitis or endocrine adverse events (AE)s Grade ≥ 2, any other non-laboratory immune-related AE ≥ Grade 3. Subjects must have minimum 9 week washout period between the last dose of anti-CTLA4 and the first dose Urelumab (BMS-663513)
    • Prior organ allograft or allogeneic bone marrow transplantation
  6. Other Exclusion Criteria

    • Prisoners or subjects who are involuntarily incarcerated
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01471210

Contacts
Contact: Recruiting sites have contact information. Please contact the sites directly. If there is no contact information, please email: Clinical.Trials@bms.com
Contact: First line of the email MUST contain NCT# and Site #.

Locations
United States, California
Local Institution Not yet recruiting
Los Angeles, California, United States, 90095
Contact: Site 0014         
Stanford University Medical Center Recruiting
Stanford, California, United States, 94305
Contact: Ronald Levy, Site 005         
United States, Indiana
Indiana University Cancer Center Recruiting
Indianapolis, Indiana, United States, 46202
Contact: Theodore Logan, Site 001    317-278-7571      
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Patrick Ott, Site 002         
United States, Michigan
Karmanos Cancer Institute Recruiting
Detroit, Michigan, United States, 48201
Contact: Radhakrishnan Ramchandren, Site 0009    313-576-8722      
United States, New Jersey
John Theurer Cancer Center Recruiting
Hackensack, New Jersey, United States, 07601
Contact: Martin Gutierrez, Site 0010    551-996-5499      
United States, New York
Memorial Sloan Kettering Cancer Center Completed
New York, New York, United States, 10065
United States, Oregon
Providence Portland Med Ctr Recruiting
Portland, Oregon, United States, 97213
Contact: Walter J Urba, Site 004         
United States, Pennsylvania
Hospital Of The University Of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Tara Gangadhar, Site 007         
United States, Virginia
University Of Virginia Health System Completed
Charlottesville, Virginia, United States, 22908
France
Local Institution Not yet recruiting
Rennes Cedex 9, France, 35033
Contact: Site 0012         
Local Institution Not yet recruiting
Villejuif, France, 94805
Contact: Site 0013         
Spain
Local Institution Recruiting
Pamplona, Spain, 31192
Contact: Site 008         
United Kingdom
Local Institution Not yet recruiting
Southampton, Hampshire, United Kingdom, SO16 6YD
Contact: Site 0018         
Local Institution Not yet recruiting
Surrey, United Kingdom, SM2 5PT
Contact: Site 0017         
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01471210     History of Changes
Other Study ID Numbers: CA186-011, 2012-000170-28
Study First Received: November 10, 2011
Last Updated: November 20, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
Spain: Agencia Española de Medicamentos y Productos Sanitarios
Spain: Institutional Review Board

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Non-Hodgkin
Neoplasms
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on November 20, 2014